The Pain Anxiety Symptom Scale: Initial Development and Evaluation of 4 and 8 Item Short Forms.

Elevated levels of anxiety in relation to chronic pain have been consistently associated with greater distress and disability. Thus, accurate measurement of pain-related anxiety is an important requirement in modern pain services. The Pain Anxiety Symptom Scale (PASS) was introduced over 30 years ago, with a shortened 20-item version introduced 10 years later. Both versions of the PASS were derived using Principal Components Analysis, an established method of measure development with roots in classical test theory. Item Response Theory (IRT) is a complementary approach to measure development that can reduce the number of items needed and maximize item utility with minimal loss of statistical and clinical information. The present study used IRT to shorten the 20-item PASS (PASS-20) in a large sample of people with chronic pain (N = 2,669). Two shortened versions were evaluated, 1 composed of the single best-performing item from each of its 4 subscales (PASS-4) and the other with the 2 best-performing items from each subscale (PASS-8). Several supplementary analyses were performed, including comparative item convergence evaluations based on sample characteristics (ie, female or male sex; clinical or online sample), factor invariance testing, and criterion validity evaluation of the 4, 8, and 20-item versions of the PASS in hierarchical regression models predicting pain-related distress and interference. Overall, both shortened PASS versions performed adequately across these supplemental tests, although the PASS-4 had more consistent item convergence between samples, stronger evidence for factor invariance, and accounted for 83% of the variance accounted for by the PASS-20% and 92% of the variance accounted for by the PASS-8 in criterion variables. Consequently, the PASS-4 is recommended for use in situations where a briefer evaluation of pain-related anxiety is appropriate. PERSPECTIVE: The Pain Anxiety Symptom Scale (PASS) is an established measure of pain-related fear. This study derived 4 and 8-item versions of the PASS using IRT. Both versions showed strong psychometric properties, stability of factor structure, and relation to important aspects of pain-related functioning.

Initial evaluation of the Chronic Pain Acceptance Questionnaire - 2.

Greater acceptance of chronic pain is associated with lesser levels of pain-related distress and disability and better overall functioning. Pain acceptance is most often assessed using the Chronic Pain Acceptance Questionnaire (CPAQ), which includes both an eight-item short form (CPAQ-8) and a twenty item parent measure (CPAQ-20). This study derived a two-item CPAQ for use in busy clinical settings and for repeated measurement during treatment, the CPAQ-2. An Item Response Theory (IRT) approach was used to identify the strongest items from the CPAQ-20, one from each of its two subscales. Next, regression analyses were conducted to evaluate the utility of the CPAQ-2 by examining variance accounted for in the CPAQ-8, CPAQ-20, and in measures of depression, pain-related fear, physical disability, and psychosocial disability. Four clinical databases were combined (N = 1,776) for the analyses. Items 9 and 14 were identified as the strongest CPAQ-20 items in the IRT analyses. The sum score of these two items accounted for over 60% of the variance in the CPAQ-8 and CPAQ-20. Furthermore, this score accounted for significant variance in measures of depression, pain-related fear, physical disability, and psychosocial disability after controlling for data collection method (i.e. in clinic or online), participant age, education, pain duration and usual pain. Finally, the amount of variance accounted for by the CPAQ-2 was comparable to that accounted for by both the CPAQ-8 and CPAQ-20. These results provide initial support for the CPAQ-2 and suggest that it is well-suited as a brief assessment of chronic pain acceptance. SIGNIFICANCE: The most frequently used measure of pain acceptance is the CPAQ, which includes both an eight-item short form, the CPAQ-8, and a longer twenty item parent measure, the CPAQ-20. The present study sought to derive a two-item measure of the CPAQ for use in busy clinical settings and for repeated measurement during treatment, the CPAQ-2. An IRT approach was used to identify the strongest items from the CPAQ-20, one from each of its two subscales in a large sample of 1,776 individuals with chronic pain. The two item measure accounted for significant variance in measures of depression, pain-related fear, physical disability, and psychosocial disability. The brief measure will be useful in assessing pain acceptance in busy clinical setting and longitudinal designs.

Integrated Behavioral Treatment for Veterans With Co-Morbid Chronic Pain and Hazardous Opioid Use: A Randomized Controlled Pilot Trial.

Opioid prescription in the treatment of chronic pain is frequent and carries a risk of increased morbidity and mortality in a clinically significant number of patients, particularly those who are using opioids in a hazardous manner. Few treatment options are available that target both pain-related interference and hazardous opioid use among patients with chronic pain. In military Veterans, this issue is of particular importance as numerous reports indicate continued high rates of opioid prescription for chronic pain, as well as significant opioid-related problems. The overall aim of the present study was to determine the feasibility of an integrated psychosocial treatment in Veterans with chronic pain, who also have evidence of hazardous opioid use. To examine this aim, a random design was used to assess the feasibility and initial efficacy of integrating 2 empirically supported interventions: Acceptance and Commitment Therapy for chronic pain and Mindfulness Based Relapse Prevention for opioid misuse. Half of participants were randomized to the integrated treatment group and all participants received usual care through a Veteran's Administration co-occurring disorders medical clinic to treat chronic pain and opioid misuse. In total, 37 participants were randomized and included in intent-to-treat analyses and 32 individuals were included in per protocol analyses with 6-month follow-up serving as the primary study endpoint. Feasibility indicators included recruitment, retention, and treatment completion rates. Recruitment fell short of targeted enrollment, although retention and completion were excellent. Primary outcome measures were opioid misuse, pain interference, and pain behavior. Simultaneous multiple regression analyses controlled for pain duration, baseline opioid dose, and baseline value for outcome measures. Results of both the intent-to-treat and per protocol indicated a significant effect in favor of the integrated intervention for opioid misuse, pain interference, and pain behavior. Results support the feasibility of providing an integrated treatment for both opioid risk and pain interference. PERSPECTIVE: Opioid misuse occurs in some opioid-prescribed individuals with chronic pain. Few treatment options exist that target both pain interference and opioid misuse. This study examined feasibility and initial efficacy of an integrated behavioral treatment for Veterans. Feasibility was supported, except recruitment. Efficacy was supported compared to usual care.

A Comparative Meta-Analysis of Unidisciplinary Psychology and Interdisciplinary Treatment Outcomes Following Acceptance and Commitment Therapy for Adults with Chronic Pain.

While much of the literature provides positive support for psychological interventions for chronic pain, 2 recent meta-analyses indicate small to moderate benefits only. This inconsistency in findings suggests that there are other treatment-related variables to consider. One possible consideration pertains to treatment format, as psychological models form the basis for both unidisciplinary psychology and integrated interdisciplinary treatments for chronic pain. Therefore, a comparative meta-analysis of unidisciplinary and interdisciplinary treatments was performed to determine whether there were differences in treatment effect size (ES) at post-treatment and follow-ups of up to 1 year. One specific treatment model, Acceptance and Commitment Therapy (ACT), was investigated as it was felt that this literature was extensive enough to perform the planned analysis, while also being circumscribed enough in size to make it feasible. In total, 29 articles met inclusion criteria, 13 reported outcomes for unidisciplinary ACT, and 15 for interdisciplinary ACT. At both post-treatment and follow-up, interdisciplinary ACT had a greater ES for physical disability, psychosocial impact, and depression compared to unidisciplinary ACT. No differences in ES were observed for pain intensity, pain-related anxiety, or pain acceptance. Findings remained the same when study heterogeneity was considered. There was a significant difference observed between treatment format and treatment duration-on average, unidisciplinary interventions were of shorter duration than interdisciplinary interventions. Moderation analyses examining the relation between total treatment duration and ES generally indicated a moderate positive relation between treatment length and ES. This relation was strong for psychosocial impact. PERSPECTIVE: A comparative meta-analysis examined the relative ES of unidisciplinary (ie, clinical psychology only) and interdisciplinary ACT for chronic pain in 29 studies. The ES for interdisciplinary ACT was larger than unidisciplinary ACT for physical disability, psychosocial impact, and depression. No differences were present for pain intensity, anxiety, and acceptance.

Patient Extratherapeutic Interpersonal Problems and Response to Psychotherapy for Depression.

OBJECTIVES: This paper aimed to synthesize empirical findings of patient extratherapeutic interpersonal variables associated with individual psychotherapy treatment outcomes in adult outpatients with depression. METHODS: A systematic search strategy was used to identify relevant studies. Thematic analysis was used to identify recurring themes in the findings. RESULTS: Forty studies met search criteria. Three themes of patient extratherapeutic interpersonal variables were identified: capacity to engage with others, capacity to navigate relationships, and capacity to achieve intimacy, progressing from basic to advanced levels of interpersonal interaction. Interpersonal variables such as interpersonal distress and style, attachment orientation, and quality of object relations were particularly useful in predicting treatment outcomes, whereas access to social support and marital status provided mixed results, likely because they do not account for relationship quality. CONCLUSIONS: Recognizing variables associated with treatment response can help clinicians identify patients at risk for nonresponse and guide efforts for adapting existing therapies and developing new ones.

Alcohol and Opioid Use in Chronic Pain: A Cross-Sectional Examination of Differences in Functioning Based on Misuse Status.

Opioid misuse is regularly associated with disrupted functioning in those with chronic pain. Less work has examined whether alcohol misuse may also interfere with functioning. This study examined frequency of opioid and alcohol misuse in 131 individuals (61.1% female) prescribed opioids for the treatment of chronic pain. Participants completed an anonymous survey online, consisting of measures of pain, functioning, and opioid and alcohol misuse. Cut scores were used to categorize individuals according to substance misuse status. Individuals were categorized as follows: 35.9% (n = 47) were not misusing either opioids or alcohol, 22.9% (n = 30) were misusing both opioids and alcohol, 38.2% (n = 50) were misusing opioids alone, and only 3.0% (n = 4) were misusing alcohol alone. A multivariate analysis of variance was performed to examine differences in pain and functioning between groups (after excluding individuals in the alcohol misuse group due to the small sample size). Group comparisons indicated that individuals who were not misusing either substance were less disabled and distressed in comparison to those who were misusing opioids alone or both opioids and alcohol. No differences were indicated between the latter 2 groups. Overall, the observed frequency of opioid misuse was somewhat higher in comparison to previous work (approximately 1 out of every 3 participants), and misuse of both alcohol and opioids was common (approximately 1 out of every 5 participants). While these data are preliminary, they do suggest that issues of substance misuse in those with chronic pain extends beyond opioids alone. PERSPECTIVE: Opioid and alcohol misuse was examined in 131 individuals prescribed opioids for chronic pain. In total, 35.9% were not misusing either, 22.9% were misusing both, 38.2% were misusing opioids, and 3.1% were misusing alcohol. Individuals not misusing either were generally less disabled and distressed compared to those misusing opioids or both.

Using Analgesics for Emotional Modulation is Associated With Increased Distress, Depression, and Risk of Opioid and Alcohol Misuse: Initial Evaluation and Component Analysis of the Reasons for Analgesic Use Measure (RAUM).

OBJECTIVES: It is important to identify aspects of analgesic use that are associated with harm in chronic pain. Historically, the focus has been patterns of use (eg, overuse). This study evaluated another aspect of use-rather than evaluating how analgesics were being used, the primary interest was in why they were being used. METHODS: In total, 334 analgesic using individuals with chronic pain responded to a pool of items assessing reasons for analgesic use. Measures of pain intensity, distress, depression, and opioid and alcohol misuse were also completed. RESULTS: Exploratory factor analyses indicated 3 overarching reasons for use, including taking analgesics: (1) for pain reduction/functional improvement; (2) for emotional modulation/sedation; and (3) to be compliant with prescriber instructions. Correlation and regression analyses indicated that the second factor had the strongest relations with the other measures used, such that greater endorsement of analgesic use for emotional modulation was associated with greater distress, depression, and opioid and alcohol misuse. Using analgesics for pain reduction/functional improvement was associated with greater pain-related distress and depression. Using analgesics to be compliant was not associated with any measure. This pattern of results was generally replicated when a subsample of 131 individuals taking opioids was examined. DISCUSSION: Results support the utility of examining reasons for analgesic use; use to achieve emotional modulation/sedation may be particularly associated with risk. The data also provide support for the questionnaire developed, the Reasons for Analgesic Use Measure.

Episodic memories of relationship quality, procedural knowledge of attachment scripts, and the experience of daughters caring for a parent with dementia.

A caregiver's attachment history with their parents may affect the thoughts, feelings, and behavior they now have as they care for a parent with dementia. Participants were 77 daughters of a parent with dementia. The nature of participant conscious episodic memories of their parental figures and unconscious procedural knowledge of caregiving processes (secure base script knowledge) were identified as two aspects of the caregiver's relationship history that may impact their involvement in care, relationship conflict, critical attitudes, and strain. Our findings indicated that the nature of episodic memories of the caregiver relationship history with parental figures were significantly associated with stress and criticism of their parent. Greater unconscious procedural knowledge of the secure base script was associated with caregiver report of less conflict and less involvement in the caregiving tasks. Potential clinical implications of this pattern are also discussed.

Using Screening Tests to Predict Aberrant Use of Opioids in Chronic Pain Patients: Caveat Emptor.

Screening tests represent a critical tool in chronic pain treatment for predicting aberrant opioid use, which has emerged as a significant public health issue. Nevertheless, there remains a significant potential for the misapplication of screeners in this context. The potential difficulties in evaluating the diagnostic efficiency of screeners have been well established, particularly with regard to the effect that the prevalence of a disorder has on predictive value. The wide range in the reported prevalence of aberrant opioid use behaviors makes it difficult to interpret data obtained from popular screeners for assessing the potential for the aberrant use of opioids. Given the prevalence of opioid problems, however, formulating clear clinical guidelines on such screeners appears highly important. The aims of the present report include: 1) providing a review of the salient issues necessary for interpreting diagnostic efficiency statistics of screening tests, 2) identifying the critical differences between sensitivity, specificity, and predictive value, and 3) discussing the characteristic effects that disease prevalence has on statistical prediction. The article also reviews key processes in screening measure development and highlights several key considerations relevant to their appropriate use in clinical decision-making. PERSPECTIVE: This article highlights common metrics for evaluating the clinical utility of screening tests in predicting aberrant opioid use. In addition, it explores a series of considerations key to developing clinical guidelines for interpreting the results of screeners in this context.

Examining Committed Action in Chronic Pain: Further Validation and Clinical Utility of the Committed Action Questionnaire.

UNLABELLED: Psychosocial treatments for chronic pain conditions, such as Acceptance and Commitment Therapy, have highlighted minimizing pain avoidance behaviors and increasing engagement in valued activities as key treatment targets. In terms of salient processes within Acceptance and Commitment Therapy, committed action is considered essential to the pursuit of a meaningful life, as it entails a flexible persistence over time in living consistently with one's values. To date, however, only 1 study has examined the association between measures of committed action and important aspects of pain-related functioning. The purpose of the present study was to analyze the reliability of the Committed Action Questionnaire (CAQ) in a sample of 149 chronic pain patients, perform a confirmatory analysis of its factor structure, and examine how CAQ scores uniquely account for variance in functioning. Confirmatory factor analyses provided support for a 2-factor model, and regression analyses, which examined the cross-sectional direct effects of the 2 subscales on health-related functioning, indicated that the CAQ accounted for significant variance in functioning after controlling for relevant covariates. Overall, these findings provide further support for the CAQ as a measure of adaptive functioning in those with longstanding pain. PERSPECTIVE: This article presents additional evidence for the reliability and validity of the CAQ with chronic pain patients. Confirmatory factor analyses provided support for the 2-factor model, with both subscales demonstrating significant associations with multiple facets of health- and pain-related functioning.

Preliminary Evaluation of the Values Tracker: A Two-Item Measure of Engagement in Valued Activities in Those With Chronic Pain.

Engagement in valued activities is an important outcome, particularly in treatments that aim to enhance quality of life in those with chronic conditions. The present study describes the initial evaluation of the Values Tracker (VT), a two-item measure of values engagement, in 302 treatment-seeking adults with chronic pain. Hierarchical regression analyses were conducted to examine the utility of the VT in the statistical prediction of pain-related functioning, after controlling for demographic variables, pain intensity, and pain-related distress. Across analyses, pain intensity accounted for significant variance (range ΔR2 = .06-.09) with pain-related distress adding additional unique variance (range ΔR2 = .07-.19). The VT accounted for additional unique variance (range ΔR2 = .02-.17) for all variables with the exception of physical disability. These findings provide initial support for the utility of the VT in those with chronic pain. Given the VT's brevity, it may be particularly useful for tracking changes in engagement in values across sessions.

Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels.

Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product.

Empathy training for resident physicians: a randomized controlled trial of a neuroscience-informed curriculum.

BACKGROUND: Physician empathy is an essential attribute of the patient-physician relationship and is associated with better outcomes, greater patient safety and fewer malpractice claims. OBJECTIVE: We tested whether an innovative empathy training protocol grounded in neuroscience could improve physician empathy as rated by patients. DESIGN: Randomized controlled trial. INTERVENTION: We randomly assigned residents and fellows from surgery, medicine, anesthesiology, psychiatry, ophthalmology, and orthopedics (N=99, 52% female, mean age 30.6 ± 3.6) to receive standard post-graduate medical education or education augmented with three 60-minute empathy training modules. MAIN MEASURE: Patient ratings of physician empathy were assessed within one-month pre-training and between 1-2 months post-training with the use of the Consultation and Relational Empathy (CARE) measure. Each physician was rated by multiple patients (pre-mean=4.6 ± 3.1; post-mean 4.9 ± 2.5), who were blinded to physician randomization. The primary outcome was change score on the patient-rated CARE. KEY RESULTS: The empathy training group showed greater changes in patient-rated CARE scores than the control (difference 2.2; P=0.04). Trained physicians also showed greater changes in knowledge of the neurobiology of empathy (difference 1.8; P<0.001) and in ability to decode facial expressions of emotion (difference 1.9; P<0.001). CONCLUSIONS: A brief intervention grounded in the neurobiology of empathy significantly improved physician empathy as rated by patients, suggesting that the quality of care in medicine could be improved by integrating the neuroscience of empathy into medical education.

Heat shock-initiated apoptosis is accelerated and removal of damaged cells is delayed in the testis of clusterin/ApoJ knock-out mice.

The secretion and localization of clusterin in the testis has led to the hypothesis that clusterin plays a role in spermatogenesis. Furthermore, the association of clusterin with apoptosis, cellular injury, disease, and regression of nongonadal tissues has led to the hypothesis that clusterin acts to protect cells from apoptosis or may be involved in tissue remodeling. To investigate the role of clusterin in the testis, we analyzed clusterin knock-out (cluKO) mice to determine the impact of the absence of clusterin on spermatogenesis. Furthermore, we investigated the cellular response to injury caused by methoxyacetic acid (MAA) toxicity and mild heat exposure in the cluKO mice to determine the extent to which clusterin protects against apoptosis or participates in tissue remodeling. We found that cluKO mice were fertile and had essentially normal spermatogenesis with the exception of some incomplete spermiation after stage VIII. No differences in testicular morphology or the incidence of apoptosis in the testis were seen between the cluKO and clusterin wild-type (cluWT) mice after MAA treatment. In contrast, apoptosis was delayed in the cluWT mice compared with the cluKO mice after heat exposure, suggesting that clusterin does have a slight protective effect against apoptosis under some conditions. Also, a dramatic loss of germ cells after heat stress occurred earlier in the cluWT testes than in the cluKO testes. Clusterin is clearly acting in a dual role in that cells can be protected from damage and dead cells can be more easily removed after some types of cellular damage but not after others.